Abstract
Purpose :
NK-4 (4,49-[3-{2-(1-ethyl-4(1H)-quinolylidene)ethylidene}pro-penylene]bis(1-ethylquinolinium iodide)) has a variety of biological activities, such as macrophage-activating, antimicrobial, anticancer properties, and is used as an immunomodulator to treat virus infection. NK-4 is also effective for treatment of cerebral ischemia and neurodegeneration. However, the effect of NK-4 on retinal neurodegenerative disease is still unknown. In this study, we tried to test whether NK-4 would have an effect on the prevention of retinal neurons from apoptosis.
Methods :
Sixteen RCS rats at 4 weeks of age were randomly assigned to four groups, with each group comprising four rats. The rats had intravitreous injection of 5 μL solution at four different concentrations of the dye, 0.1 mg/mL, 0.01 mg/mL, 0.001 mg/mL, and 0.0001 mg/mL, in the left eyes of each group, with a 30-gauge-needle-attached Hamilton syringe. DMSO solution injection at the same volume served as control in the right eyes of each group. The rats were housed under a 12-hour light/dark cycle for 14 days. Apoptosis was detected in frozen sections of the eyes, and also stained immunohistochemically for glial fibrillary acidic protein (GFAP), protein kinase C alpha (PKC-α). The immunochemically stained areas were compared by the Image J software.
Results :
The number of apoptotic cells decreased and the thickness of outer nuclear layer was thicker in the retina of dye-injected eyes, compared with vehicle-injected eyes, under 12-hour light/dark cycle. GFAP-stained areas showed a decrease in the retina of dye-injected eyes, compared with vehicle-injected eyes. The areas with PKC-α staining also showed difference between the dye-injected and saline-injected eyes.
Conclusions :
NK-4 injection has a potential role for suppressing the apoptosis of photoreceptor, reducing GFAP expression in retinal Müller cells, and helping prevent rod bipolar cell dysfunction in RCS rats. Additional experiments are under way to investigate the mechanism for preventing apoptosis of photoreceptor after NK-4 injection.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.